Patent GB-740076-A (GB)
Title: The production of lactones
Inventor: LACEY RICHARD NORMAN
IPC: C07D307/58
Filed: 1951-06-20
Abstract: A process for the production of unsaturated lactones comprises treating the acetoacetic acid ester of a hydroxy-carbonyl compound of the formula <FORM:0740076/IV(a)/1> <FORM:0740076/IV(a)/2> <FORM:0740076/IV(a)/3> or <FORM:0740076/IV(a)/4> where X represents the acetoacetic acid residue (CH3.CO.CH2CO-), R1 represents an alkyl, aryl or substituted aryl group, R2 represents hydrogen or an alkyl, aryl or substituted aryl group, R3 and R6 represent alkyl groups or hydrogen, R4, R5, R7 and R8 represent alkyl groups, and R9 represents the atoms necessary to complete, with the -C=C- group, an aromatic nucleus, under such conditions that one molecular proportion of water is eliminated therefrom.  The products are of the formul <FORM:0740076/IV(a)/5> <FORM:0740076/IV(a)/6> <FORM:0740076/IV(a)/7> and <FORM:0740076/IV(a)/8> respectively.  The invention also comprises, as new substances, compounds of the formula (E) where R1 and R2, when aryl, are unsubstituted, and compounds of the formul (G) and (H).  Alkyl groups mentioned are methyl, ethyl, propyl, butyl, amyl, hexyl, heptyl, octyl, nonyl, decyl, hendecyl, lauryl and stearyl groups.  As aryl and substituted aryl groups are mentioned phenyl, methylphenyl, nitrophenyl, chlorophenyl, dimethylphenyl and nitro-methylphenyl groups.  The elimination of water from the acetoacetic acid esters may in some cases be brought about by adding an entraining agent with a boiling-point in the range 80 DEG  to 150 DEG  C. such as benzene, toluene or xylene and distilling the water from the mixture as an azeotrope.  The speed of the lactone formation may be increased by the addition of a weakly basic catalyst, e.g. an amine such as triethylamine, pyridine or piperidine, salts of such amines with weak organic acids, e.g. sodium acetate.  The elimination of water may also be effected by treating the ester with a basic catalyst for the reaction of a carbonyl group with a reactive methylene group, e.g. an alkali alkoxide or a salt such as potassium carbonate, sodium cyanide, sodium sulphite, alkaline anion exchange resins and alkali or alkaline earth metal hydroxides, suitably at temperatures up to about 60 DEG  C.  The acetoacetic acid esters can be prepared by the reaction of diketene with compounds of the formula (A), (B), (C) and (D) where X represents a hydrogen atom. The aceto-acetic acid ester produced need not be isolated and it is possible to carry out the process by slowly adding diketene below the surface of a boiling mixture of the hydroxy carbonyl compound and a weakly basic catalyst in an inert organic solvent which acts as an entrainer.  The acetoacetic acid ester which first forms then eliminates water which is removed as an azeotrope.  Compounds of the formula (A) in which R1 is a methyl group and X is hydrogen can be obtained by hydrating ethynyl carbinols of the formula R2R3C(OH).C­CH in the presence of mercuric salts.  The corresponding acetoacetic esters may be produced similarly by reacting the ethynyl carbinol with diketene and hydrating the ester in the presence of mercuric salts.  In examples: (1) diketene and diacetone alcohol are reacted to give diacetone alcohol aceto-acetate, which on treatment below 25 DEG  C. with alcoholic potassium hydroxide gives the lactone of 4 : 6-dimethylhept - 3 - en - 6 - ol - 2 - on - 3 - carboxylic acid; (2) the lactone of 4-methylhex-3-en-5-ol-2-on-3-carboxylic acid is obtained by slowly adding diketene below the surface of a boiling mixture of acetoin, toluene and dimethylamine while distilling off water; (3) the lactone of 4-ethylhept - 3 - en - 5 - ol - 2 - on - 3 - carboxylic acid is prepared similarly from propionoin; (4) butyroin and diketene are reacted to give a mixture of the acetoacetic acid ester and the lactone of 4-propyloct-3-en-5-ol-2-on-3-carboxylic acid; (5) the same lactone as in (4) is obtained using the method of example (2); (6) 4-hendecylhexadec-3-en-5-ol-2-on-3-carboxylic acid lactone is prepared as in (2) from lauroin; (7) 4 : 5 - diphenylpent - 3 - en - 5 - ol - 2 - on - 3 - carboxylic acid lactone is obtained similarly from benzoin; (8) 2 : 21-dimethylhex-3-en-1-ol-5-on-4-carboxylic acid lactone is prepared similarly from 2 : 21-dimethylpropan-1-ol-3-al; (9) 3-acetyl-coumarin is prepared from salicylaldehyde; (10) 4-methyl-3-aceto coumarin is prepared similarly from o-hydroxy-acetophenone; (11) the acetoacetic acid ester of butyroin produced as in (4) on standing with aqueous sodium hydroxide gives 4-propyloct-3-en-5-ol-2-on-3-carboxylic acid lactone; (12) 2 : 21-dimethylpropan-1-ol-3-al is reacted with diketene to give the acetoacetic ester which on standing with aqueous sodium hydroxide gives the same lactone as in example (8); (13) phenacyl alcohol and diketene are reacted to give phenacylacetoacetate which is converted to 4-phenylpent-3-en-5-ol-2-on-3-carboxylic acid, (a) by heating with toluene with azeotropic distillation of water, and (b) by warming at 50 DEG  C. with methanolic sodium hydroxide; (14) diketene and but-1-yn-3-ol are reacted to give the acetoacetate which on refluxing with an aqueous/ethanolic solution of mercuric chloride gives acetoin acetoacetate, and the latter on refluxing in toluene with piperidine yields the lactone of 4-methylhex-3-en-5-ol-2-on-3-carboxylic acid; (15) 5 : 5 : 7-trimethyloct-3-en-6-ol-2-on-3-carboxylic acid lactone is prepared by a similar method to (2) from isobutyraldol and diketene.  The products of (1) to (4), (8), (10) and (15) are converted to their 2 : 4-dinitrophenylhydrazones, and that of (1) also to its semicarbazone.  The products may be hydrogenated to tetrahydrofurans and pyrans or converted to a -methyl b -furoic acids by the method of Specification 740,077.  Some of the products have antibiotic activity and insecticidal action and inhibit the growth of animal tissues, seed germination and plant growth.